tbuckley/cabot-search huggingface dataset:
Impact of TKI combination therapy and MRD negativity on outcomes in Philadelphia chromosome-positive ALL: A retrospective, single-center experience.
Authors: Valerie Tran, Ian Michael Bouligny, Yanal Mufeed Alnimer, Kyle Zacholski, Chad Michael Venn, Thuy Ho, Keri Renee Maher
Journal: Journal of Clinical Oncology (2022)

e19052 Background: Presence of the Philadelphia chromosome (Ph+) in newly diagnosed B-cell acute lymphoblastic leukemia (ALL) conveys high-risk disease and a poor prognosis. Hematopoietic stem cell transplant (HSCT) following induction and achievement of remission remains the standard of care. In the era of TKIs targeting BCR-ABL1 in addition to newer combination strategies, the impact of HSCT in the first complete remission (CR) remains unclear, particularly in the context of measurable residual disease (MRD) negativity. We present the outcomes of Ph+ B-ALL patients with and without HSCT, stratified with respect to MRD negativity. Methods: We identified 32 patients with Ph+ B-cell ALL from January 2015 to January 2021 at our institution who were treated with TKIs and received HSCT with evaluable MRD prior to transplant. Baseline patient demographics were obtained, including labs, performance status at diagnosis, comorbidities, molecular profiling by NGS, doses of induction, toxicities, response, MRD analysis by PCR, HCT-CI scores, and HSCT outcomes. The event for calculating the overall survival (OS) was the date of death. Patients were otherwise censored at the date of last contact. Results: Of the 25 patients who underwent HSCT, the median age was 46 years and 48.0% were male. TKIs in combination with high-intensity regimens were given in 88.0% of patients at induction. There were no deaths within 60 days following induction. Twenty (80.0%) patients achieved CR or CRi, and of those, 56% were MRD-negative by the time of HSCT. At a median follow-up time of 4.74 years, the OS of patients that achieved CR following induction and HSCT was not reached, and there were no significant differences between the two groups (p = .1326). We then compared the 14 MRD-negative patients undergoing HSCT to 7 MRD-negative patients who did not undergo transplant aged ≤65 years with ECOG ≤2. There was no difference in age (p = .5353), ECOG score (p = .6364), or Charlson Comorbidity Index score (p = .7018) between the two groups. The median OS in the MRD-negative HSCT group was not reached and the median OS in the MRD-negative non-HSCT was 5.45 years (p = .0210). Conclusions: In the era of combination chemotherapy with TKIs, MRD positivity at the time of allogenic HSCT does not appear to impact survival at 5 years in this small retrospective cohort. Post-transplant TKI maintenance may abrogate MRD implications at the time of HSCT. Our findings demonstrate that Ph+ ALL patients benefit from HSCT when candidates, regardless of MRD status, as those undergoing HSCT demonstrated a statistically superior survival. HSCT appears to remain the standard of care despite newer combination strategies and MRD-driven treatment.
COVID-19 vaccine and incidence of severe immune-mediated adverse events in patients with renal cell carcinoma (RCC) on checkpoint inhibitor immunotherapy (CPI).
Authors: Danielle Gilbert, Junxiao Hu, Elizabeth R Kessler, Elaine T. Lam
Journal: Journal of Clinical Oncology (2022)

e16509 Background: Immune-mediated adverse events (irAEs) can be seen in patients (pts) receiving checkpoint inhibitors (CPI). It is unknown whether the immune response to vaccines against Sars-CoV-2 interacts with the immune activation from CPI therapy. In this retrospective study, we examined the incidence of severe irAEs in pts with renal cell carcinoma (RCC) who received vaccines against Sars-CoV-2 during the course of their CPI therapy. Methods: Following IRB approval, RCC pts who received any CPI treatment since FDA authorization of the first COVID-19 vaccine in March 2021 were identified via institutional electronic health record. Pts who received one or more doses of an authorized vaccine within 60 days of CPI treatment were included. The primary endpoint was to evaluate the incidence of severe irAE (defined as one or more of the following: grade 3 AE or above, multi-system involvement, need for hospitalization). Secondary endpoints included time between CPI and vaccination, need for immunosuppressive therapy, and rate of discontinuation. Data was analyzed using descriptive statistics. Results: Sixty-five pts were included in our analysis with a median age of 66 years (IQR: 58.0, 73.0); 80% pts were male. At the time of vaccination, 26 pts (40.0%) received CPI monotherapy, 12 pts (18.4%) received combination (combo) CPI therapy, and 27 pts (41.6%) received combo therapy with a tyrosine kinase inhibitor (TKI) and CPI. The type of vaccine received was Pfizer Bio-N-Tech in 30 pts (46.2%), Moderna in 33 pts (50.7%), and Johnson and Johnson in 2 pts (3.1%). Six pts received only one vaccination (9.2%), 18 pts received two vaccinations (27.7%), and 40 pts received 3 or more vaccinations (61.5%). Eleven pts (16.9%) experienced severe irAEs following vaccination. Rates of severe irAEs was 3.8% (1/26) with CPI monotherapy, 25% (3/12) with combo CPI, and 25.9% (7/27) with combo CPI and TKI. Severe irAEs occurred after the first vaccine dose in 4 pts (36.4%), second dose in 3 pts (27.3%), and third dose in 4 pts (36.4%) pts. The median time between CPI treatment and vaccination in this group was 11.0 days (IQR: 7.5-15.5). Hospitalization was required for 6 patients (54.5%). Ten pts (90.9%) required immunosuppressive therapy with a median steroid duration of 85.5 days (IQR 36.8, 176.0). Six pts (54.5%) discontinued CPI therapy following severe irAEs. Conclusions: In this retrospective study, the observed rate of severe irAEs in RCC patients who received CPI and COVID-19 vaccine concomitantly was similar to historical controls, suggesting that there is no definite increase in the incidence of severe irAEs in pts undergoing CPI therapy and receiving COVID-19 vaccination. Future confirmatory studies are warranted. Supported by the Health Data Compass Data Warehouse project (healthdatacompass.org)
Clinical utility of tumor next-generational sequencing (NGS) panel testing to inform treatment decisions for patients with advanced solid tumors.
Authors: Lucia Bogdan, Ramy R. Saleh, Lisa Avery, Samanta Del Rossi, Celeste Yu, Philippe L. Bedard
Journal: Journal of Clinical Oncology (2022)

3119 Background: There is limited information about the clinical utility of targeted NGS panel testing to inform decision-making for patients with advanced solid tumors. The Ontario-wide Cancer Targeted Nucleic Acid Evaluation (OCTANE) is an ongoing prospective study that enrolled over 4,500 solid tumor patients for NGS panel testing. We performed a retrospective survey of 21 medical oncologists enrolling OCTANE patients at a single academic institution to evaluate the impact of NGS testing on treatment decisions. Methods: Patients and treating oncologists were identified at the Princess Margaret Cancer Centre between 2016-2021. Tumor-only sequencing was performed using a custom hybridization capture panel of 555 cancer genes (Hi5) or a commercial 161-gene amplicon DNA/RNA panel (Oncomine Comprehensive v3). Oncologists were asked to review testing results for individual patients and complete a survey indicating whether NGS testing impacted treatment decisions. Mutations were defined as actionable based on clinical judgment and compared to classifications provided by OncoKB, an FDA-recognized precision medicine knowledgebase. The primary outcome of this study was rate of treatment change based on mutation results. Patient, test, and physician factors were evaluated for association with treatment changes using univariate analyses and a mixed effects model. Results: Two cohorts were surveyed, the first between 2017-2019 and the second in 2021. Of the 582 surveys sent, 394 (67.7%) were completed. Each physician completed a median of 19 surveys (range, 9-48). We found that 188 (47.7%) patients had a mutation classified as actionable by the oncologist, of whom 134 (71.3%) had ≥1 OncoKB-defined actionable mutation(s). 62/394 (15.7%) patients were matched to a treatment, of whom 37 were enrolled in a clinical trial, 13 received an approved drug, 4 were prescribed off-label therapy and 8 avoided ineffective treatment. 127/188 (67.5%) patients with actionable mutations did not receive treatment due to lack of available therapy, stability on current regimen, clinical deterioration or patient decision. Rate of treatment change was highest for bowel (15/37, 40.5%), breast (14/52, 27.5%), biliary tract (6/22, 27.3%) and lung (4/17, 23.5%) cancers. Treatment decisions were not associated with patient age, gender, physician clinical experience, physician gender, testing experience, OncoKB mutation level or time from biopsy to sequencing. There was no difference in overall survival between patients with matched vs. no matched treatment ( p = 0.55, median survival not reached). Conclusions: OCTANE testing led to a change in drug treatment in 15.7% of patients, supporting the clinical utility of NGS panel testing for patients with advanced solid tumors. Patient, test, and physician characteristics were not significantly associated with treatment change.
A novel risk-scoring model developed based on tertiary lymphoid structure related genes predict the prognosis and immunotherapeutic efficacy in cutaneous melanoma.
Authors: Bin Wang, Jie Liu, Yu Jiang
Journal: Journal of Clinical Oncology (2022)

e13574 Background: Emerging evidence has proven that tertiary lymphoid structures (TLSs) are predictive biomarkers of favorable clinical outcomes in melanoma, whereas the exact role of TLS-related genes remained unclear. In the present study, we aimed to establish a novel risk-scoring model based on TLS-related genes to predict the prognosis and immunotherapeutic efficacy in cutaneous melanoma. Methods: Patients in the TCGA-SKCM cohort (n = 468) were clustered into two subtypes based on the prognosis-related genes associated with TLSs though consensus clustering analysis, and differentially expressed genes were screened between two clusters. By univariate and the least absolute shrinkage and selection operator (LASSO) Cox regression analysis, a 13-gene signature was selected to construct a prognostic risk-scoring model. The median risk score served as the unified cutoff to divide patients into high- and low-risk groups. GSE65904 (n = 220) and GSE544467 (n = 79) cohorts were used for external validation. Univariate and multivariate cox analysis were used to select significant variables for construction of nomogram. The nomogram model was evaluated by concordance index, time-dependent receiver operating characteristics (ROC) curve, calibration curve and decision curve analysis (DCA). GSEA, CIBERSORT, Tumor Immune Dysfunction and Exclusion (TIDE) and Immunophenoscore (IPS) were utilized to explore the potential mechanism of immune-related process and immunotherapy. Results: Thirteen signature genes (CCL8, DLX3, CNTFR, CNFN, BCAN, CD33, HAPLN3, ABCB1, CLIC2, GCNT1, FGF1, A2ML1, GBP2) were developed to construct a risk-scoring model. Melanoma patients could be grouped into high- and low-risk groups, and low-risk patients showed better survival than high-risk patients. Area under the curve values of 1, 3, and 5 years were 0.76, 0.72, and 0.73 in the training set, respectively, indicating a good predictive efficacy. In addition, based on independent prognostic factors including risk score, age, stage, T and N Staging after univariate and multivariate Cox regression analyses, a nomogram was constructed to better estimate individual survival. For the prediction of 1, 3, and 5-year overall survival probability according to the nomogram, the area under the receiver operating characteristic curve was 0.81, 0.80 and 0.76, respectively. Furthermore, we explored the correlation of the prognostic risk-scoring model with tumor microenvironment (TME) and immunotherapeutic efficacy. Patients in the low risk group featured immunoactive TME, higher IPS scores and lower TIDE scores, and was regarded as the potential beneficiaries of immunotherapy. Conclusions: The 13-gene risk score proposed in the research may provide new insights into the individualized evaluation of cutaneous melanoma prognosis and Immunotherapeutic Efficacy
Prevalence of pain symptoms among U.S. adult cancer survivors.
Authors: Xinwen Hu, Chao Cao, Yunan Han, Shu Jiang, Lin Yang, Graham A. Colditz
Journal: Journal of Clinical Oncology (2022)

12062 Background: Pain symptoms are common in cancer survivors. The life expectancy of US cancer survivors continues to raise. To date, the comprehensive pattern of pain symptoms in US cancer survivors by cancer history remains unknown. Methods: Data on pain symptoms and correlates were derived from a nationally representative sample of cancer survivors (n = 55,716, weighted population = 17,352,886) in the 1997-2018 National Health Interview Survey. Individuals who answered “yes” to the questions “During the past three months, did you have headache/facial/neck/low back pain/low back pain radiating to the leg” were considered as having pain symptoms at respective anatomical regions. The US national prevalence of pain overall and by anatomical regions were estimated. Correlates of pain symptoms were examined using multivariable logistic regression. Results: The prevalence of overall pain symptoms was persistently high (48.5%, 95% CI: 48.0-49.0) in cancer survivors from 1997-2018 ( P for trend =.58), driven by low back (37.6%, 95% CI: 37.1-38.0) and neck pain (20.9%, 95% CI: 20.5-21.3), and was leading in survivors of bone (63.1%, 95% CI: 57.9-68.4), soft tissue (58.1%, 95% CI: 50.6-65.6), and brain (58.2%, 95% CI: 52.3-64.0) cancers. Considerable pain symptoms were reported by survivors of commonly diagnosed cancers: lung (48.5%), breast (46.7%), colon (52.2%) and prostate (38.4%) cancers. The prevalence of pain is higher in females (52.9%) than males (42.6%) across all anatomical regions (OR, 1.50 [95% CI, 1.38-1.63]), particularly headache (19.8% vs. 8.6%) and facial pain (8.6% vs. 3.9%). Of note, females with reproductive system cancers, cervical (66.3%), uterine (60.0%) and ovarian (59.4%) cancers, have a higher prevalence in all types of pain than those with other cancers. Cancer survivors aged ≥65 years were less likely to report pain symptoms than younger survivors (OR, 0.71 [95% CI, 0.64-0.79]). Despite no racial disparity in the prevalence of overall pain, Non-Hispanic Blacks (18.6%, 95% CI: 17.2-20.0) and Hispanics (21.2%, 95% CI: 19.5-22.9) were more likely to report headache than Non-Hispanic Whites (14.4%, 95% CI: 14.0-14.8). A higher prevalence of pain symptoms was consistently observed in cancer survivors with low income, smoking history, low physical activity levels, diabetes, and cardiovascular diseases (all P &lt;.05). Age at cancer diagnosis ( P for trend &lt;.001), but not the time since, affected pain symptoms. Cancer survivors diagnosed at age 0-14 (53.0%, 95% CI: 49.1-56.9) and 15-39 years (58.6%, 95% CI: 57.5-59.7) had a significantly higher prevalence of pain across all anatomical regions than those at ≥40 years (45.5%, 95% CI: 44.9-46.1). Conclusions: Half of US cancer survivors experienced pain symptoms, driven by low back and neck pain. Higher prevalence of pain was noted in cancer survivors with younger age, female sex, low income and suboptimal lifestyle behaviors, calling for adequate pain management in cancer survivorship.
A prospective decision impact study to evaluate the utility of the Oncotype DX Breast DCIS score assay in selecting patients with ductal carcinoma in situ (DCIS) following breast conservation surgery (BCS) for radiotherapy.
Authors: Mitchel Barry, Siun Walsh, Sinead Kelly, Maurice Stokes, Anne Gribbin, Michael A. Maher, Malcolm R. Kell
Journal: Journal of Clinical Oncology (2022)

e12571 Background: There is increasing reliance on data provided by genomic risk assessment assays to guide therapeutic decisions. The objective of this prospective study was to assess the impact of the Oncotype DX Breast DCIS Score assay on radiation treatment recommendations in patients with DCIS undergoing BCS. Methods: This decision impact study is a prospectively enrolled observational study of newly diagnosed patients (n = 135) following BCS for removal of DCIS of all grades 30mm or less with clear margins (i.e. 2 mm or normal re-excised margins). Only patients who were candidates to receive radiation therapy were considered. Fifteen patients withdrew from the study or had insufficient volume of DCIS for assay analysis. Radiation Oncologists were blinded to the Oncotype DX Breast DCIS Score assay prior to recording their recommendation for radiotherapy or not. IRB approval was granted following review of study protocol and informed consent was obtained from all patients. Results: Among 120 patients tested, the Oncotype DX Breast DCIS Score assay determined that 58/120 (48.3%) of patients had a low score (LS) (0-38), 30/120 (25%) had an intermediate score (IS) (39-54) and 32/120 (26.7%) had a high score (HS) (&gt;55). The Oncotype DX Breast DCIS Score assay concurred with the Radiation Oncologists recommendation to proceed with radiation treatment in 96.7% of patients (i.e. 60/62 patients with an IS or HS). The Oncotype DX Breast DCIS Score assay altered treatment decisions in 12.5% (4/32) of patients with a HS and in 7.1% (2/28) patient with an IS. In patients where the Oncotype DX Breast DCIS Score assay altered treatment recommendation all had a low volume (i.e. less than 10mm) of high/intermediate grade DCIS with an IS or HS. Conclusions: This study demonstrates that Oncotype DX Breast DCIS Score assay accurately supports the selection of patients with DCIS for radiation treatment and equally can be helpful in selecting a subgroup of patients with small volumes of intermediate/high grade DCIS who can potentially avoid radiotherapy.
Clinicians’ perspective on use of immune checkpoint inhibitors and related biomarkers for solid tumors.
Authors: Kaitlynn Moser, Klaus Lindpaintner, Michelle Soto, Daniela Geba, Paul Allen
Journal: Journal of Clinical Oncology (2022)

e13643 Background: Immune checkpoint inhibitors (ICIs) are a valuable treatment option for patients with malignant tumors, but only selected patients respond to ICIs. Available biomarkers are of limited use in guiding ICI therapy. We sought to examine clinicians’ perspective on the use of ICIs and biomarkers for treatment of malignant tumors and to identify unmet needs related to their use. Methods: We conducted in-depth telephone interviews of eight oncologists, and 100 oncologists completed online surveys. Results: Oncologists have a positive attitude toward use of ICIs, and 98% of them prescribe them in all approved indications. Clinicians report that only about half of the patients with solid tumors responded to treatment, overestimating the response rate to ICIs across most types of tumors they treat, compared with data in the literature. They ranked the lack of reliability of biomarkers to guide treatment (rating of 4.4 out of 7) as the top challenge with use of ICIs, followed by lack of overall efficacy and toxicity or occurrence of immune-related adverse events. The biomarkers most often used by survey participants were: a comprehensive panel including driver mutations and tumor mutational burden (69% of respondents), programmed cell death ligand-1 (PD-L1) expression (62%), and microsatellite instability (MSI) (56%). Oncologists indicated that they ordered biomarkers for each type of cancer according to their perceived usefulness of each biomarker in predicting the outcomes for ICI therapy, being more likely to use those perceived as useful or very useful. Conclusions: Clinicians indicate that more reliable therapy-response prediction biomarkers would have a great impact on treatment decisions for patients with solid tumors, reducing unnecessary treatments, side effects, and health care expenditures.
Toxicities of anti-VEGF therapies used in metastatic renal cell carcinoma: A real-world experience.
Authors: Samip R. Master, Dawood Findakly
Journal: Journal of Clinical Oncology (2022)

e16533 Background: Tumor endothelial proliferation inhibition using vascular endothelial growth factor-tyrosine kinase inhibitors (VEGF-TKIs) have revolutionized metastatic renal cell carcinoma (mRCC) therapy. We retrospectively analyzed data on various anti-VEGF adverse events (AEs) utilizing the FDA Adverse Events Reports System (FAERS). Methods: We examined the FAERS public dashboard data on VEGF inhibitors’ reported AEs for the years 2019-2021. Data analyzed using descriptive statistics. Results: A total of 34,651 AEs were identified for anti-VEGF therapies, of which 29,328 (84.6%) were serious and 5,830 (16.82%) reported deaths (Table). Lenvatinib has most reported serious hemorrhagic events and thyroid impairment in 5.5% and 1.2%, respectively, and least (3.4%) reported dermatologic toxicity (including Hand-foot skin reaction, depigmentation, and rash. Cabozantinib has most (2.8%) reported gastrointestinal (GI) perforation and fistula. Pazopanib has most bone marrow suppression (BMS)—neutropenia, leukopenia, thrombocytopenia, and anemia (43.3%), dermatologic toxicity (25.8%), hepatotoxicity—jaundice, elevated transaminases, hyperbilirubinemia, hepatic encephalopathy, coagulopathy, ascites, and/or hepatorenal syndrome (23.9%), arterial thromboembolic events (ATE)—comprising cerebral infarction, ischemic stroke, transient ischemic attack, myocardial infarction, angina (19.8%), proteinuria and nephrotic syndrome (NS; 10.4%), pulmonary toxicity—interstitial lung disease, and pneumonitis (7.2%), posterior reversible encephalopathy syndrome (PRES; 4.9%), cardiotoxicity—cardiac failure (3.1%), and tumor lysis syndrome (TLS; 0.9%). Sunitinib has most reported osteonecrosis of the jaw AEs (ONJ; 37.3%), QT Prolongation and various arrhythmias (11.9%), severe hypertension (SHTN—including accelerated, urgency, and emergency; 10.0%), and aortic complications—including aortic aneurysm, dissection, and rupture (3.1%). Conclusions: Pazopanib has most while axitinib has least reported BMS, ATE, and pulmonary AEs. Cabozantinib has most reported GI AEs and sunitinib has most reported ONJ, SHTN, QT prolongation, arrhythmias, and aortic complications. With expanding treatment landscape for mRCC, this study helps shed light on the different anti-VEGF toxicity profiles and would therefore support treatment decision making.